Innate immunity receptors Flashcards
what is a PRR? What does it detect? What expresses it?
pattern recognition receptor expressed on both innate and adaptive immune cells. It recognizes PAMPS and DAMPS
What is a DAMP? Example?
danger associated molecular pattern –> these are self (host) molecules that are found in places they are not supposed to be (through apoptosis)
in contrast PAMPS are from foreign agents
t or f, a foreign macro molecule is a PAMP
false, the macro molecule may contain PAMPS but is not a PAMP itself.
what occurs when a PAMP / DAMP binds with a PRR?
when a pattern recognition receptor binds a PAMP / DAMP the immune system activates. Often cytokines are the first things to be released which act as instant messengers.
what are the main pro-inflammatory cytokines?
IL-6
TNF-alpha
IL-1
alpha dominates therefore pro - inflammatory
+ other small numbers
what are the main anti-inflammatory cytokines?
IL-10
TGF-beta
beta is weak, therefore anti-inflammatory + big number
t or f, toll like receptors are examples of pattern recognition receptors (PRR’s)
true
where are TLR’s located and what do they bind?
TLR’s can be found on the surface of cells or inside cells.
they bind both PAMPS and DAMPS
Explain the structure of TLR receptors.
they look like a hook. They have tail imbedded into a membrane and poking out on the other side.
the hook structure sticks out and is made of leucine - rich repeats which is important for ligand interaction
explain endosomal TLR’s verses PM TLR’s.
an endosomal TLR will be embedded into a endosome within the cell. The hook structure then sticks into the endosome.
a PM TLR will have its hook leucine structure stick away from the cell into the ECF
What does TLR 4 recognize?
TLR 4 recognizes LPS of gram negative bacteria
What is the signal pathway of TLR 4?
LPS binds with a co-factor called CD-14. This complex interacts with TLR 4 which induces a conformational change. this causes
MyD88 —> NF-kB –> alters transcription of cytokine production. typically pro-inflammatory
after TLR 4 binds LPS, what changes occur within the cell? (2/3)
- NF-kB is produced which causes increased production of cytokines.
- cytokines recruit other cells and modulate inflammation
- proteins expressed on the cell surface also alter –> e.g. more MHC may be expressed for Ag presentation to T cells.
true or false, dendritic cells have TLR’s.
true. e.g. a dendritic cell will use TLR 4 to recognize LPS of a gram negative bacteria. Phagocytosis will occur and the dendritic cell will express the antigen on MHC receptors (which TLR 4 induced). The dendritic cell will take this to lymph nodes and present it to T cells.
what does TLR 7 recognize?
single stranded RNA
where does TLR 7 detect ssRNA? explain how this occurs if ssRNA comes from a virus?
most viruses that enter a cell are engulfed into endosome’s. Now in an endosome, the ssRNA can be presented to endosomal TLR’s (in this case TLR 7).
TLR 7 wont detect nuclear or cystolic RNA.
What is the signal pathway for TLR 7 once it has bound endosomal ssRNA?
The tail of TLR 7 will be in the cystol. After binding occurs
MyD88 –> series of conversions –> activation of type one interferon genes (IFN)
true or false, TLR’s are always monomeric.
false, they can form hetero and homo dimers.
what are the two common type one IFN’s? what can they do?
alpha and beta IFN
they can block virus replication and also act as messengers to other cells to prepare for an infection.
what are NOD -like receptors (NLR’s) ? what do they bind and where are they found?
NOD = nucleotide-binding oligomerization domain
NLR’s are found freely in the cytoplasm. They bind bacterial ligands, often break down products of peptidoglycan.
what is a NLR’s signal pathway?
bacterial ligand binds NLR which causes NF-kB production. This goes and induces cytokine gene activation.
What are RIG-I-like helicase receptors (RLH)?
RIG-I = retinoic acid inducible gene one
they are free floating cytoplasm receptors that recognize viral RNA
RLH, TLR, and NLR receptors are all PRR’s correct?
yes, all pattern recognition receptors
why don’t RLH receptors bind our own RNA in the cytoplasm?
because our RNA is Capped with the 5’ cap and poly A tail. Viral RNA is not and this is detected by RLH.
what does the binding of viral RNA to RLH cause in the cell?
the activation of type one IFN genes.
true or false, TLR 7 is found in the plasma membrane and TLR 4 is found in the endosome.
false, TLR 4 is found in the PM where it detects LPS
TLR 7 is found in endosome’s where it detects ssRNA
true or false, TRL 4 requires additional proteins to bind LPS.
true, it needs LPS binding protein and CD-14
note: TLR 7 doesn’t use additional proteins, it interacts with ssRNA directly
